title: Update in the medical therapy of Cushing's disease.
abstract: OBJECTIVE
  Recently developed agents treat Cushing's disease by inhibiting ACTH secretion from corticotrope tumors or antagonizing cortisol action.
  
  
  RESULTS
  The dopamine agonist cabergoline and the somatostatin agonist pasireotide target ACTH secretion. Each has low rates of normalization of urine-free cortisol (UFC), about 40% at doses of 1-7 mg weekly and 20% at doses of 600 or 900 μg twice daily, respectively. Cabergoline, an oral agent, has a relatively benign side-effect profile, primarily asthenia. Small trials suggest that combination therapy with ketoconazole increases effectiveness. Pasireotide, a parenteral agent, is associated with types and rates of adverse events similar to those seen with other somatostatin agonists (diarrhea, nausea, cholelithiasis), except for glucose intolerance, which occurs more frequently (∼75%). It may be most effective when UFC is less than two-fold normal. A few case reports suggest that pasireotide or cabergoline may control tumor size and ACTH secretion from macroadenomas. Retinoic acid must be evaluated further. The glucocorticoid antagonist mifepristone ameliorates glucose intolerance but may not normalize other Cushingoid features.
  
  
  CONCLUSIONS
  These novel approaches provide options for treatment of patients in whom surgery has failed or is not possible, and those who decline adrenalectomy or radiation therapy.
authors.affiliation: Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Building 10, CRC, 1 East, Rm 1-3140, 10 Center Dr, MSC 1109, Bethesda MD 20892-1109, USA. NiemanL@nih.gov
authors.forename: Lynnette K
authors.initials: LK
authors.lastname: Nieman
mesh_terms: D000077465:Cabergoline; D018491:Dopamine Agonists / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004873:Ergolines / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D013004:Somatostatin; C517782:pasireotide; D000077465:Cabergoline; D006854:Hydrocortisone